title: Preparation, characterization, pharmacokinetics, and bioactivity of honokiol-in-hydroxypropyl-β-cyclodextrin-in-liposome.
abstract: Entrapping inclusion complexes in liposomes has been proposed to increase the entrapment efficiency (EE) and stability of liposomes compared with conventional liposomes. In the present study, a stable honokiol-in-hydroxypropyl-β-cyclodextrin-in-liposome (honokiol-in-HP-β-CD-in-liposome) was developed as honokiol delivery system by a novel method. The final molar ratio of honokiol/HP-β-CD/lipid was selected as 1:2:2. The mean particle size was 123.5 nm, the zeta potential was -25.6 mV, and the EE was 91.09 ± 2.76%. The release profile in vitro demonstrated that honokiol is released from honokiol-in-HP-β-CD-in-liposome with a sustained and slow speed. Crystallographic study indicated that honokiol was first bound within HP-β-CD and then the inclusion complex was encapsulated within liposomes. Honokiol-in-HP-β-CD-in-liposome without freeze dry kept stable for at least 6 months at 4°C. Pharmacokinetic study revealed that honokiol-in-HP-β-CD-in-liposome significantly retarded the elimination and prolonged the residence time in circulating system. The data of bioactivity showed that honokiol-in-HP-β-CD-in-liposome remained similar antiproliferative activity in A549 and HepG2 tumor cells compared to free honokiol. These results suggested that we had successfully prepared honokiol-in-HP-β-CD-in-liposome. The novel honokiol formulation was easy to push industrialization forward and might be a potential carrier for honokiol delivery in tumor chemotherapy.
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China; Tianjin Medical University Cancer Institute and Hospital, Department of Lymphoma, Tianjin 300060, China.
authors.forename: Xianhuo
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Linyu
authors.initials: L
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Chongyang
authors.initials: C
authors.lastname: Deng
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Xingmei
authors.initials: X
authors.lastname: Duan
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: lijuan17@hotmail.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000295:instrumentation / Q000379:methods; D004355:Drug Stability; D056945:Hep G2 Cells; D006801:Humans; D007275:Injections, Intravenous; D017705:Lignans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D008081:Liposomes; D008297:Male; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D004337:Drug Carriers; D017705:Lignans; D008081:Liposomes; D047392:beta-Cyclodextrins; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols